The proposed studies aim to determine the neurobiological mechanisms governing the function of neuronal networks in the cerebral cortex, and the mechanisms responsible for use-dependent plasticity in these networks. An understanding of these mechanisms can be attained by revealing the biophysical, neurochemical and morphological characteristics of the various classes of cortical neurons, and the synaptic interactions that link them to form functional circuits. These studies will focus on intrinsic circuits that are responsible for the vast majority of cortical synapses, and have a critical role in cortical function, both in shaping the response properties of cortical neurons and in use dependent plasticity. The studies will focus on the representation, within the somatosensory cortex, of the mystical vibrissae: the whiskers on rodents' snouts. This cortical area, the "barrel cortex," contains discrete representations of individual whiskers, and offers unique opportunities to decipher general principles of functional organization in the cerebral cortex. These advantages are conferred by the unique morphological features of the barrel cortex that enable the visualization of individual whisker representations in unstained, live tissue. This provides a means of accurately identifying specific functional columns in an in vitro preparation, and for predicting the response properties of individual neurons within these columns. The first aim of this project is to test the hypothesis that specific classes of neurons form specific patterns of intrinsic synaptic interactions, and display unique biophysical features, and that these characteristics are responsible for shaping the receptive field properties of cortical neurons. For this purpose, specific classes of projection (excitatory) and local-circuit (inhibitory) neurons will be identified in vitro slice preparation, and recorded from intracellularly to reveal their biophysical membrane properties. The different classes of neurons will then be injected with biocytin to reveal their morphological attributes, particularly the arborizations of their local axon collaterals within individual barrel columns and between different columns. This approach will elucidate the contribution of specific classes of cells to the synaptic circuitry mediating the functional organization of the barrel contribution of specific classes of cells to the synaptic circuitry mediating the functional organization of the barrel cortex. The second aim of this project is to test the hypothesis that alterations in intrinsic synaptic interactions are responsible for plasticity in the barrel cortex induced by sensory derivation. This will be accomplished by daily clipping of all but a group of whiskers in newborn rodents until they reach adulthood. This will be accomplished by daily clipping of all but a group of whiskers in newborn rodents until they reach adulthood. This procedure alters the response properties of neurons in barrel columns representing the deprived and the spared vibrissae. By examining the effects of this sensory manipulation on the patterns of intrinsic connections and the biophysical properties of barrel cortex neurons, it will be possible to determine the mechanisms responsible for this plasticity. These studies will provide data pertinent to understanding the normal functions of the cerebral cortex and the processes underlying congenital or acquired neurological disease.